Hormone Suppression May Be Why High-Protein Weight-Loss Diets Work

Action Points

Explain to interested patients that this study found that ingesting proteins had the greatest suppressive effect on ghrelin, a hormone that stimulates appetite.

Explain also that this study found that carbohydrates initially suppressed ghrelin levels, but then they rebounded to above baseline values.

SEATTLE, Jan. 18 -- Proteins are better at suppressing the appetite-stimulating hormone ghrelin than carbohydrates and lipids, a finding that may lead to new, specially designed weight-loss diets, researchers here suggested.

Consumption of all three macronutrient classes was associated with significant, but varying, reductions in total ghrelin (P<0.0001) and acyl ghrelin (P<0.001) levels compared with baseline, Karen E. Foster-Schubert, M.D., of the University of Washington, and colleagues, reported online in the Journal of Clinical Endocrinology & Metabolism.

But ingesting protein had the greatest effect on both total ghrelin and acyl ghrelin levels over six hours, followed by carbohydrates, and, lastly, lipids. The researchers measured depth and duration of suppression by calculating the decremental area-under-the-ghrelin-curve (D-AUC).

Ghrelin is thought to influence hunger around mealtime, the researchers said, because levels increase before meals and are suppressed by food intake. Understanding how different macronutrients affect ghrelin levels "could facilitate rational design of weight-reducing diets," they suggested.

So the researchers recruited 16 healthy volunteers (seven men and nine women, mean age 34) who had a body mass index of less than 30 kg/m2, had been weight-stable for the preceding six months, and were within 2.5 kg of their lifetime maximum weight.

The study consisted of three six-hour sessions separated by at least one week. Before each session, the participants refrained from eating for 12 hours and exercising for 24 hours. All 16 participants completed the three study visits.

At each session, participants drank a beverage designed to contain calories equal to 20% of each participant's total daily energy expenditure. The beverages contained 80% of the type of macronutrient being evaluated at that particular visit -- proteins, carbohydrates, or lipids -- and 10% each of the other two.

The researchers took three blood samples at baseline and then one every 20 minutes for six hours after beverage consumption to measure acyl and total ghrelin levels.

Using visual analog scales, the participants rated how hungry or full they felt 20 minutes before the intervention and every 40 minutes thereafter.

Fasting baseline plasma levels of ghrelin and acyl ghrelin were equivalent at all three study visits.

Protein also had the most pronounced suppressive effect on total ghrelin levels over six hours with a D-AUC of 72 hr%, followed by carbohydrate (56 hr%) and, lastly, lipid (38 hr%).

When the researchers looked at just the first three hours after beverage consumption, they found that carbohydrates had a more pronounced suppressive effect than did proteins.

In the last three hours after drinking the carbohydrate beverage, however, both acyl and total ghrelin levels rebounded significantly above baseline values (P<0.001).

This difference between the first and second halves of the study period did not occur with protein or lipid, both of which suppressed acyl and total ghrelin levels until study completion, the researchers said.

"Our finding of a rebound of total and especially acyl ghrelin above baseline following high-carbohydrate meals could provide some physiologic basis for claims made by low-carbohydrate diet advocates that ingesting carbohydrates prompts an early hunger rebound," the authors wrote.

However, the type of macronutrient had no significant effect on the visual analog scale appetite measures, a consequence, perhaps, of technical difficulties some participants had with the computerized reporting system, the researchers said.

One possible explanation presented by the authors to explain the spike in acyl and total ghrelin levels following carbohydrate ingestion is the faster gastric emptying following carbohydrate consumption compared with that of protein or lipid.

"The prolonged suppression observed following lipids and proteins might relate to their prolonged emptying from the stomach, causing more sustained activation of post-gastric ghrelin-suppressing mechanisms," they said.

The authors acknowledged several limitations of the study, including its small size and the fact that the test meals were not typical foods, being liquid and consisting of very large balanced differences in macronutrient composition.

They also noted the difficulty some participants had with the hunger reporting system.

The researchers concluded that, "although the mechanisms by which specific macronutrients regulate circulating ghrelin are not fully known, our results could help explain the ability of high-protein diets to cause weight loss as well as the tendency for high-fat diets to promote weight gain."

This study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

Dr. Foster-Schubert received support from the National Center for Research Resources.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

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